PROJECT SUMMARY Acute withdrawal from chronic alcohol exposure is associated with a number of symptoms including neuronal hyperexcitability, heightened irritability, and a negative affective state. In addition, acute withdrawal is associated with escalated and uncontrolled alcohol consumption, which is thought to occur, at least in part, due to negative reinforcement as drinking alleviates withdrawal symptoms. The brain undergoes significant neuroadaptations during withdrawal from chronic alcohol exposure. These neuroadaptive processes are thought to play an important role in driving maladaptive behaviors including continued alcohol consumption. During the current funding period CARE investigators have uncovered a number of significant, epigenetically regulated changes in gene expression in the brains of rats withdrawn from chronic ethanol exposure. Interestingly, while some withdrawal-induced epigenetic modifications appear to be common throughout the brain, many are brain region- specific. CARE investigators have further demonstrated that reversal of some of these epigenetic alterations attenuates withdrawal symptoms including those associated with negative affect and altered neurotransmission. However, it is not yet known whether withdrawal-induced epigenetic dysregulation promotes escalated alcohol consumption. The proposed Behavioral Core will allow CARE investigators to address this gap by providing the resources necessary to link withdrawal-induced epigenetic changes with alterations in drinking behavior across all four Research Projects of the CARE. The Behavioral Core will provide CARE investigators with oversight of experimental design, implementation, and analysis of standardized behavioral experiments measuring operant ethanol self-administration in control and ethanol withdrawn rats following either systemic or region-specific reversal of withdrawal-induced epigenetic alterations. The Behavioral Core will also facilitate centralized production of brain tissue from control rats and rats withdrawn from chronic ethanol liquid diet for experiments conducted by the Epigenetics Core. The results generated by the Behavioral Core will allow CARE investigators to establish a causal link between epigenetic modifications and escalated alcohol consumption. Together with findings from each Research Project, these data will inform future work aimed at the development of novel drugs targeting epigenetic factors for the treatment of alcohol use disorders.